2. Academic Validation
  3. Metabolic regulation of RNA methylation by the m6A-reader IGF2BP3

Metabolic regulation of RNA methylation by the m6A-reader IGF2BP3

  • bioRxiv. 2024 Nov 3:2024.10.31.621399. doi: 10.1101/2024.10.31.621399.
Gunjan Sharma 1,  Martin Gutierrez 2,  Anthony E Jones 3,  Amit Kumar Jaiswal 1,  Zachary T Neeb 2,  Amy Rios 3,  Michelle L Thaxton 1,  Tasha L Lin 4,  Tiffany M Tran 1 5,  Lyna E S Kabbani 2,  Alexander J Ritter 2,  Linsey Stiles 3 5,  Johanna Ten Hoeve 3 6,  Ajit S Divakaruni 3,  Jeremy R Sanford 2 7,  Dinesh S Rao 1 8 9
Affiliations

Affiliations

  • 1 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA.
  • 2 Department of Molecular, Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California Santa Cruz, Santa Cruz, CA.
  • 3 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, United States.
  • 4 Division of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • 5 Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
  • 6 UCLA Metabolomics Center, University of California, Los Angeles, CA, 90095, USA.
  • 7 Center for Biomolecular Science & Engineering, University of California Santa Cruz, Santa Cruz, CA.
  • 8 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA.
  • 9 Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA.
PMID: 39554138 DOI: 10.1101/2024.10.31.621399
Abstract

The interplay of RNA modifications - deposited by "writers", removed by "erasers" and identified by RNA binding proteins known as "readers" - forms the basis of the epitranscriptomic gene regulation hypothesis. Recent studies have identified the oncofetal RNA-binding protein IGF2BP3 as a "reader" of the N6-methyladenosine (m6A) modification and crucial for regulating gene expression. Yet, how its function as a reader overlaps with its critical oncogenic function in leukemia remains an open question. Here, we report the novel finding that the reader IGF2BP3 reprograms cellular metabolism, resulting in an altered ability of the "writers" to modify the epitranscriptome. In leukemia cells, IGF2BP3 supports increased glycolytic flux and one-carbon metabolism, leading to increased production of S-adenosyl methionine (SAM), a key substrate for methylation reactions within the cell. IGF2BP3 directly regulates the translation of MAT2B, the regulatory subunit of the methionine-adenosyltransferase complex, which is the final enzyme in a pathway leading to SAM production. This, in turn, results in increased m6A modifications on RNA, resulting in positive feedback regulation. This novel mechanism illustrates how metabolism mutually acts with epitranscriptomic modifications, underscoring the pervasive impact of IGF2BP3 in gene regulatory mechanisms governing a broad range of cancer-specific processes.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z